Source Localization and Possible Causes of Interictal Epileptic Activity in Tumor-Associated Epilepsy

Patt, Stephan; Steenbeck, J.; Hochstetter, Albrecht; Kraft, Robert A.; Huonker, R.; Haueisen, Jens; Haberland, N.; Ebmeier, Kristian; Hliscs, Rudolf; Fiehler, Jens; Nowak, H.; Kalff, Rolf

doi:10.1006/nbdi.2000.0288

Cited by 55 publications

(34 citation statements)

References 25 publications

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“…It is known that neurons from cortex adjacent to tumors display abnormal electrophysiology, with an increase in spontaneous activity under resting conditions (37). This observation could explain why, in patients with gliomas, epileptic seizures often persist even after removal of the primary tumor (38,39). It is possible that the physiological changes elicited in the tumor cells aberrantly modulate synaptic transmission of adjacent neurons through glia͞neuronal networks (11,12).…”

Section: Discussionmentioning

confidence: 99%

Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

Maas

Patt

Schrey

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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345

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In mammals, RNA editing by site-selective adenosine deamination regulates key functional properties of neurotransmitter receptors in the central nervous system. Glutamate receptor subunit B is nearly 100% edited at one position (the Q͞R-site), which is essential for normal receptor function. Its significance is apparent from mouse models in which a slightly reduced rate of Q͞R-site editing is associated with early onset epilepsy and premature death. Here we report that in tissues from malignant human brain tumors, this editing position of glutamate receptor subunit B is substantially underedited compared with control tissues. We also observe alterations in editing and alternative splicing of serotonin receptor 5-HT 2C transcripts. These changes correlate with a decrease in enzymatic activity of the editing enzyme adenosine deaminase acting on RNA (ADAR) 2, as deduced from analysis of ADAR2 self-editing. Our results suggest a role for RNA editing in tumor progression and may provide a molecular model explaining the occurrence of epileptic seizures in association with malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

Maas

Patt

Schrey

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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345

317

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“…The results of these studies suggested that epileptiform activity originates within the peritumoral border, 1-2 mm away from the tumor mass. 16,29,32 In addition, the pattern of NR2B phosphorylation in the tissue in the mouse model of glioma is different from that in human patients with glioma. First, we observed an obvious difference in the glioma cell distribution within the peritumoral region between the implanted tumors in the mouse model and those of de novo tumors in patients.…”

Section: Discussionmentioning

confidence: 96%

“…The results of recent studies conducted both in patients with a glioma and in rodents implanted with a glioma have suggested that epileptiform activity originates within the peritumoral border, 1-2 mm away from the tumor mass, where invading tumor cells surround neurons. 16,29,32 A recent clinical study measured the glutamate (Glu) concentrations of dialysates taken from the peritumoral cortex or from an uninvolved area of the brain. The results demonstrated peritumoral Glu concentrations higher than 100 mM, which is 100-fold higher than the levels in uninvolved brain.…”

mentioning

confidence: 99%

Phosphorylation of NMDA 2B at S1303 in human glioma peritumoral tissue: implications for glioma epileptogenesis

Gao

Wang

Cai

et al. 2014

FOC

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Object Peritumoral seizures are an early symptom of a glioma. To gain a better understanding of the molecular mechanism underlying tumor-induced epileptogenesis, the authors studied modulation of the N-methyl-d-aspartate (NMDA) receptor in peritumoral tissue. Methods To study the possible etiology of peritumoral seizures, NMDA receptor expression, posttranslational modification, and function were analyzed in an orthotopic mouse model of human gliomas and primary patient glioma tissue in which the peritumoral border (tumor-brain interface) was preserved in a tissue block during surgery. Results The authors found that the NMDA receptor containing the 2B subunit (NR2B), a predominantly extrasynaptic receptor, is highly phosphorylated at S1013 in the neurons located in the periglioma area of the mouse brain. NR2B is also highly phosphorylated at S1013 in the neurons located in the peritumoral area from human brain tissue containing a glioma. The phosphorylation of the extrasynaptic NMDA receptor increases its permeability for Ca2+ influx and subsequently mediates neuronal overexcitation and seizure activity. Conclusions These data suggest that overexcitation of the extrasynaptic NMDA receptors in the peritumoral neurons may contribute to the development of peritumoral seizures and that the phosphorylated NR2B may be a therapeutic target for blocking primary brain tumor–induced peritumoral seizures.

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“…Tumors may cause changes of neurotransmitter balance (increased glutamine and decreased γ-aminobutyric acid concentrations), synaptic receptors, and ion channels, resulting in an increased epileptogenicity of the surrounding neocortex [87]. Patt et al [98] performed a systematic MEG study in patients with various brain tumors and found a correlation between histopathology and the distance between dipole localizations and the tumor boundary. Glioma patients showed epileptic activity closer to the tumor boundary (or even within the tumor) than patients with mixed glioneural tumors or metastasis.…”

Section: Brain Tumorsmentioning

confidence: 99%

Magnetoencephalography in presurgical epilepsy evaluation

et al. 2002

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The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has led to a major breakthrough of MEG in presurgical epilepsy evaluation. Localizations of the interictal spike zone with MEG showed excellent agreement with invasive electrical recordings, were useful to clarify the spatial relationship of the irritative spike zone to structural lesions, and could attribute epileptic activity to lobar subcompartments both in temporal lobe and extratemporal epilepsy. MEG was especially useful for the study of patients with non-lesional neocortical epilepsy and of patients with large lesions, where it provided unique information on the epileptogenic zone. It could reliably localize sensorimotor cortex prior to surgical procedures adjacent to central fissure. MEG language mapping yielded concordant results with the Wada test and cortical stimulation studies. MEG localizations of epileptic activity and essential brain regions were successfully integrated into frameless stereotaxy systems providing accurate functional information intraoperatively. Because MEG and EEG yield both complementary and confirmatory information, combined MEG-EEG recordings in conjunction with advanced source modeling techniques will further improve the noninvasive evaluation of epilepsy patients and constantly reduce the need for invasive procedures.

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Source Localization and Possible Causes of Interictal Epileptic Activity in Tumor-Associated Epilepsy

Cited by 55 publications

References 25 publications

Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

Phosphorylation of NMDA 2B at S1303 in human glioma peritumoral tissue: implications for glioma epileptogenesis

Magnetoencephalography in presurgical epilepsy evaluation

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